Office of Research Humane Endpoints for Laboratory Animals - Office of Research

Humane Endpoints for Laboratory Animals

  • Purpose:

The purpose of this document is to provide guidelines for selecting an endpoint that reduces animal pain and/or distress, while still meeting research objectives when animals are used for biomedical research, teaching, and testing. These guidelines are provided to assist investigators in fulfilling their ethical responsibilities to minimize animal pain and/or distress. Investigators are expected to consult with Campus Veterinary Services or a clinical veterinarian affiliated with the facility to assist with developing these endpoints, and for additional information or questions. In this document “endpoint” refers to one or a combination of physical (e.g., body weight), behavioral (e.g., grooming activity), or other signs of disease or distress that are used, typically during a longitudinal experimental procedure in which animal health may deteriorate (e.g., inoculation with an infectious agent), and to decide when an intervention will be terminated or an animal may be euthanized to minimize pain or distress.


  • Background:


Although it is crucial to minimize the level of pain and distress experienced by laboratory animals, it is also important that the scientific objectives of experimental studies are achieved. The criteria that provides the basis for terminating experimental procedures in order to minimize or alleviate any actual or potential pain, distress, or discomfort is made by choosing the earliest endpoint that is compatible with the scientific objectives; these criteria are referred to as humane endpoints. Selection of such endpoints by the investigator involves consultation with CAMPUS Veterinary Services or the facility clinical veterinarian(s), and the endpoints chosen must be approved by the IACUC. For additional reference material, the ILAR Journal, volume 41, is devoted to this topic1.


The principles of humane endpoints apply to all species. Humane endpoints for species or specific projects that may not be covered in this document are determined on a case-by-case basis in consultation with Campus Veterinary Services or the facility clinical veterinarian(s).



  • Guidelines


  • General Humane Endpoints:


The following are general humane endpoints that require euthanasia:


  1. The inability to reach food or water for approximately 12 hours.
  2. A 20% decrease in optimal body weight
  3. A Body Condition Score (attachments 1-6) typically less than a 2 on a 5-point scale or less than a 3 on a 9-point scale for adult animals.
  4. Development of conditions that result in significant pain that cannot be alleviated by analgesics.


Prior approval from the IACUC is required if an investigator wishes to maintain an animal on study when endpoints meet the above criteria. Obtaining such approval requires scientific justification.


General observations for assessing pain and distress include change in body weight, external physical appearance, clinical signs (e.g., inability to reach food and water, lethargy or decreased mental alertness, labored breathing, inability to remain upright), significant changes in behavior, and responses to external stimuli.  Sick animals should be identified as early as possible prior to a moribund state (e.g., near death). Laboratory personnel must carefully observe the animals for changes in health status, appearance, and behavior, and have knowledge of the animal treatment(s) and procedures that are part of the approved IACUC protocol.  Animals should be weighed and the weight documented on a frequency to ensure the animals to not exceed 20% weight loss.


During periods when morbidity and mortality are expected to increase, animals must be evaluated a minimum of two times daily (approximately 6 hours apart including an AM and PM observation during the vivarium’s lights on cycle). Those animals that are not expected to survive until the next scheduled evaluation should be humanely euthanized.


Humane endpoints will vary depending on the nature of the study. Protocols may include more specific criteria. Investigators requesting departures from these standard endpoints must discuss with Campus Veterinary Services or the facility clinical veterinarian(s). Identifying the initial signs that occur prior to a moribund state in order to avoid additional pain and suffering is key to developing humane endpoints. Criteria with a scoring system provide an excellent, objective method for identifying the appropriate time for euthanasia, and can be developed with the assistance of Campus Veterinary Services or the facility clinical veterinarian(s) for individual projects. Objective criteria are best when they can be uniformly applied by a variety of personnel. A Body Condition Score is one example of the type of assessment for inclusion in such a scoring system. The attached references are general guidelines for Body Condition Score assessment.  Should an animal appear ill or unthrifty Campus Veterinary Services or the facility clinical veterinarian(s) must be contacted for further assessment.


Pilot studies will provide an opportunity to evaluate humane endpoints and assure the scientific objectives are met before proceeding to large scale projects.


UC Davis facilities, such as non-human primate facilities, have more specific criteria and guidelines for euthanasia that must be approved by the IACUC prior to implementation.


  • Death as an Endpoint:


If an animal must be allowed to die without intervention in order to answer a scientific question, this is considered “death as an endpoint”.

Death as an endpoint is not typically necessary for research protocols but may be required in some situations, including acute toxicity testing, assessment of virulence of pathogens, and neutralization tests for toxins.


Death as an endpoint requires scientific justification and documentation in the IACUC protocol that the above humane endpoints cannot be used.  Such justifications may include reference to the requirements of regulatory agencies (e.g., EPA, FDA).


  • Tumor Burden:


General guidelines regarding tumor burden should be followed.  Euthanasia is indicated if the total tumor burden is greater than or equal to 10% of the animal’s normal body weight, or any single tumor exceeds 2 cm in size in any direction for mice or 4 cm for rats, a diminished Body Condition Score, the tumor prevents ambulation or ability to reach food and water, the tumor is ulcerated, necrotic or infected, or the tumor is causing significant pain and distress. Certain tumor therapies under investigation may result in an expected progression of tumor necrosis, ulceration, and/or healing; this must be addressed in the approved IACUC protocol. If the tumor is infected the clinical veterinary service will recommend either euthanasia or antibiotic treatment based on the animal’s health status and study needs.


Premature euthanasia may result in the loss of valuable information regarding the success of novel studies and therapies. Pilot studies may be used to establish individual humane endpoints for therapeutic studies for cancer-related research.


  • Euthanasia:


If the veterinary staff has examined an animal and determined that it will not survive until the next scheduled examination, a reasonable effort will be made to contact the Principle Investigator (P.I.) or their designee to obtain permission to treat or euthanize the animal.  If the veterinary staff is unable to contact the P.I. or designee, the clinical veterinarian, clinical veterinary service, or Attending Veterinarian will be contacted to obtain permission to euthanize the animal.


It is important for investigators to promptly respond to all veterinary communications. If immediate euthanasia is not indicated and an animal is deemed stable by the clinical veterinarian(s) then a plan for further monitoring or intervention (such as implementing analgesics, antibiotics, diagnostics, etc.) as needed will be instituted.

  • ILAR Journal V41(2) 2000.
  • Ullman-Cullere MH, Foltz CJ. Body condition scoring: a rapid and accurate method for assessing health status in mice. Lab Anim Sci 49:319-323, 1999
  • United Kingdom Coordinating Committee on Cancer Research (UKCCCR). Guidelines for the Welfare of Animals in Experimental Neoplasia (2nd ed). Br Cancer 77: 1-10, 1998

Humane Endpoints for Laboratory Animals 1

Attachment 1

Humane Endpoints for Laboratory Animals 2

Attachment 2

Humane Endpoints for Laboratory Animals 3

Attachment 3

Humane Endpoints for Laboratory Animals cat body conditioning

Attachment 4

Humane Endpoints for Laboratory Animals 4

Attachment 5

Humane Endpoints for Laboratory Animals 5

Attachment 6

Procedure: IACUC-28
Date: January 12, 2017
Enabled By: PHS
Supersedes: February 11, 2016